Updated project metadata.
Organoid technology provides the possibility to culture human colon
tissue and patient-derived colorectal cancers (CRC) while maintaining
all functional and phenotypic characteristics. Labeling of human colon
stem cells (CoSCs), especially in normal and benign tumor organoids, is
challenging and therefore limits usability of multi-patient organoid
libraries for CoSC research. Here, we developed STAR (STem cell Ascl2
Reporter), a minimal enhancer/promoter element that reports
transcriptional activity of ASCL2, a master regulator of LGR5+ CoSC
fate. Among others via lentiviral infection, STAR minigene labels stem
cells in normal as well as in multiple engineered and patient-derived
CRC organoids of different stage and genetic make-up. STAR revealed that
stem cell driven differentiation hierarchies and the capacity of cell
fate plasticity (de-differentiation) are present at all stages of human
CRC development. The flexible and user-friendly nature of STAR
applications in combination with organoid technology will facilitate
basic research on human adult stem cell biology.